What evidence is there that ME/CFS is more autoimmune than chronic infection?

[SOC]

This vagus nerve infection / sickness behavior theory of ME/CFS is the only one so far that, theoretically at least, explains the entire disease process from initial infection, all the way up to the final end symptoms (or at least most of the symptoms).

That's a definitive statement that I don't think you've backed up with solid evidence. It does not explain many aspects of ME/CFS. It can certainly explain some aspects of ME/CFS, and possibly most of the aspects of ME/CFS for some patients, but it hardly explains everything.

Most importantly, it does not convincingly explain the defining characteristic of ME/CFS -- PEM/PENE as described in the ICC. Yes, I know you think it does, but your argument is based on defining PEM as exercise intolerance and extended fatigue, which is not very convincing. Show me evidence that sickness behavior results in failed 2-day CPET tests and I might be more willing to accept your theory.

 

[adreno]

Michael VanElzakker hypothesizes that many of the symptoms of ME/CFS simply arise out of sickness behavior. In other words, our ME/CFS symptoms are sickness behavior. Sickness behavior and ME/CFS symptoms are one and the same. I am going for reiterative overkill here to get the point across!

Thank you for your lecture. Now I'll explain something for you.

Non-specific symptoms (or behaviors) means they are observed across a range of diseases and disorders. Since this range of diseases has different etiologies, it is not possible to infer the underlying cause of disease from these symptoms. In other words, the symptoms do not differentiate one disease from another.

You can speculate all you want about "vagus nerve infection" in ME, but it is irrelevant to the point. There is no way to infer the cause of ME from sickness behavior in patients. The expression of those behaviors in patients does not tell us whether the patients have cancer, infection, autoimmune disease, or even just depression.

Saying that ME is sickness behavior does not add anything useful to our understanding. Sickness behavior is not a disease, but simply a range of behaviors, that can be described in different ways, and have different underlying etiologies. So claiming that ME = sickness behavior is equal to claiming that ME = range of unspecific behaviors.

And to top the cake, the Hornig/Lipkin study showed that the cytokine profile of ME patients does not even match the cytokine profile commonly observed in sickness behavior, which makes it even more irrelevant.

 

[halcyon]

Just to play devil's advocate, we've been placing a lot of weight on the Lipkin study but we shouldn't forget that it's a single, unreplicated study and has some limitations.

 

[lansbergen]

Sickness behavior is not a disease, but simply a range of behaviors, that can be described in different ways, and have different underlying etiologies.

I agree

 

[MeSci]

And this about Stephen Holgate: Stephen refers to ME/CFS as ‘a spectrum of disorders’ and has said that looking for the cause is a lost cause (Nature Reviews: Neuroscience 2011).

Yes, it really sounds as if he has an open mind about all the potential causes of ME.

He certainly does - see this thread.

 

[MeSci]

Nope, here's a screenshot from the paper in question:

View attachment 11139

TNF-a wasn't presented in a figure but the table says there was a non-significant statistical trend toward lower score in the ME/CFS group compared to controls.

Sorry again if this has already been said, but I think it was uncertain how long these patients had been ill, so it wasn't possible to know whether there was a distinctly different cytokine pattern between patients ill <3 years and those ill >3 years, as there was in the plasma study. The plasma study showed significant drops in many cytokines after the first 3 years.

 

[Jonathan Edwards]

Jonathan,

for us neophytes, would you expand on your statement about Dr. Chi is biopsies looking extremely normal in structure? dr. Chia is one clinician who has taken his own time and money to investigate a possible tirgger/cause of ME/CFS, only to be ignored by the research community and I've often wondered why.

I am just making the point that although Chia's pictures show the apparent presence of virus RNA or protein, the structure of the tissue where the staining is looks normal - and I think Dr Chia would expect people to read it as normal, otherwise there would be comment on the structural abnormality.

If the virus was inducing production of TNF or IL-1 locally then leucocytes should have noticed and congregated in the tissue (these cytokines are strongly chemoattractive, by upregulating blood vessel stickiness for the white cells).

My assumption was that the suggestion was that this virus was a quiescent reservoir, supplying virus to cause problems elsewhere. However, I have not read or listened to Dr Chia's most recent analysis. I hope to be able to do that this month and talk to him in person.

I will say that in the context of persistent presence of infection Dr Chia does seem to have a lot more controlled evidence than most of the other theories. With regard to why his theory is ignored - so far I have made enquiries amongst people who worked in the virology environment that the early UK papers come from and the view seemed to be that finding enteroviruses does not take you very far in the end - you can find them in a lot of normal people. However, I would like to look at the detail a bit more. The real question is whether or not there are a group of jigsaw pieces that fit together or whether in fact the group of bits that look as if they are all the lady's hat are in fact unrelated bits of other people's hats in the background that have nothing to do with each other - as so often happens in this game.

 

[Sidereal]

Sorry again if this has already been said, but I think it was uncertain how long these patients had been ill, so it wasn't possible to know whether there was a distinctly different cytokine pattern between patients ill <3 years and those ill >3 years, as there was in the plasma study. The plasma study showed significant drops in many cytokines after the first 3 years.

Right, this sample wasn't broken down into <3 years vs >3 years.

 

[Hip]

That's a definitive statement that I don't think you've backed up with solid evidence. It does not explain many aspects of ME/CFS. It can certainly explain some aspects of ME/CFS, and possibly most of the aspects of ME/CFS for some patients, but it hardly explains everything.

I think my statement is correct though, from the theoretical angle. I am not referring to empirical evidence, which as yet there is none for VanElzakker's theory (it will require post-mortem studies to provide empirical evidence); rather I am talking about his theory being the first all-encompassing theoretical biomedical model of ME/CFS that I have come across.

Out of all the ME/CFS theories that you have read over the years, have you ever come across any theory that offers an explanation of the entire ME/CFS disease process from beginning to end, tracking all the biochemical mechanics from the initial infection, right to the end symptoms of ME/CFS?

VanElzakker's theory provides a model to understand the entire biochemical route, detailing how a viral infection can ultimately lead the end symptoms of ME/CFS. Whether this theory turns out to be right or wrong, in any case, it is quite astounding that it offers this explanatory scope. That just that scope in itself makes it very interesting as a theory.

Can you think of any other ME/CFS biomedical model with the same scope? Let me know if you find one.

Most importantly, it does not convincingly explain the defining characteristic of ME/CFS -- PEM/PENE as described in the ICC. Yes, I know you think it does, but your argument is based on defining PEM as exercise intolerance and extended fatigue, which is not very convincing. Show me evidence that sickness behavior as seen in many other illnesses results in failed 2-day CPET tests as shown in ME/CFS and I might be more willing to accept your theory.

What I said was: there is enough there to suggest that PEM may well be a sickness behavior symptom, but that more research would be needed. Perhaps we need to search through more literature on cancer sickness behavior symptoms, and examine more closely the PEM they get. The authors of the Maes study stated that they think PEM probably also occurs during sickness behavior.

And note that it would not matter if the PEM in cancer was not as severe, or not quite the same, as the PEM in ME/CFS. These are different diseases, so their precise manifestations may vary a little. The nature and severity of PEM varies greatly even among ME/CFS patients.

In ME/CFS, I would guess that one reason the PEM can be more severe than the PEM of cancer is because in ME/CFS, exercise could well lead to viral reactivation (in the vagus), which I expect would greatly worsen the PEM by worsening the sickness behavior. Whereas this cannot happen in cancer.



And although I said earlier that sickness behavior likely cannot explain the OI manifestations in ME/CFS, I forgot to mention that nevertheless, the vagus nerve infection hypothesis as a whole may well be able to explain OI.

The following explanation is my idea, not VanElzakker's, but I think it is possible that a vagus nerve infection might cause the OI:

Think about it: the vagus nerve is the central nerve of the parasympathetic side of the autonomic nervous system. So if this nerve is infected, as Michael VanElzakker posits, not only could this infection trigger sickness behavior, but conceivably, the infection might also render the nerve dysfunctional (via triggering an autoimmune attack on the nerve, for example), which then gives rise to dysautonomia and thus orthostatic intolerance (OI) symptoms.

So this is where the vagus nerve infection becomes very interesting: this infection may cause both sickness behavior, which explains the bulk of ME/CFS symptoms, and also OI, which covers the remaining ME/CFS symptoms.


I know these are early days for VanElzakker's theory, and I know there is no evidence to support my conjecture that a vagus infection might cause the dysautonomia and OI in ME/CFS; but I am just attempting to show that the vagus infection theory is potentially consistent with every symptom seen in ME/CFS.

And it is an eminently testable theory: once post-mortem studies are performed, so that the vagus nerve in ME/CFS patients can be checked for infection, we will know whether VanElzakker's theory is right or wrong.

Thank you for your lecture.

My pleasure.

Did you fall asleep during the lecture though, and miss all the salient details! You seem to be raising points that have already been covered.

 

[adreno]

Did you fall asleep during the lecture though

I'll admit to nodding off once or twice.

 

[Scarecrow]

Sorry again if this has already been said, but I think it was uncertain how long these patients had been ill, so it wasn't possible to know whether there was a distinctly different cytokine pattern between patients ill <3 years and those ill >3 years, as there was in the plasma study. The plasma study showed significant drops in many cytokines after the first 3 years.

Right, this sample wasn't broken down into <3 years vs >3 years.

I think they looked at the short and long term cases but didn't see the same elevated / decreased pattern that they found in plasma. I think that either Hornig or Lipkin commented. I'll post the link if I find it.

 

[Mij]

What I said was: there is enough there to suggest that PEM may well be a sickness behavior symptom, but that more research would be needed. Perhaps we need to search through more literature on cancer sickness behavior symptoms, and examine more closely the PEM they get. The authors of the Maes study stated that they think PEM probably also occurs during sickness behavior.

And note that it would not matter if the PEM in cancer was not as severe, or not quite the same, as the PEM in ME/CFS. These are different diseases, so their precise manifestations may vary a little. The nature and severity of PEM varies greatly even among ME/CFS patients.

It would be interesting to know why some of us don't develop PEM until 6-7yrs into the illness, such as myself, even during the acute viral phase. Sickness behaviours are an acute adaptive mechanism.

 

[SOC]

And note that it would not matter if the PEM in cancer was not as severe, or not quite the same, as the PEM in ME/CFS. These are different diseases, so their precise manifestations may vary a little. The nature and severity of PEM varies greatly even among ME/CFS patients.

In ME/CFS, I would guess that one reason the PEM can be more severe than the PEM of cancer is because in ME/CFS, exercise could well lead to viral reactivation, which I expect would greatly worsen the PEM. Whereas this cannot happen in cancer.

This is not a quantitative issue -- more or less severe. This is a qualitative issue. Exercise intolerance and fatigue, which is what is seen in cancer, is not the same thing as PEM. Cancer patients can exercise and benefit from it. CPET tests are commonly done on cancer without adverse effects. The CPET result abnormalities seen in ME/CFS patients are not reported in cancer patients. See Cardiopulmonary exercise testing in cancer rehabilitation: a systematic review.

Our results suggest that CPET is feasible and seems to be safe for patients with cancer prior to a physical exercise programme.

Your position that the exercise intolerance/fatigue seen in many different conditions is equivalent to ME/CFS PEM is akin to saying that men's and women's bodies are equivalent. Yes, there are multiple similarities -- one head, two arms, two legs, brain, kidneys, lungs, nervous system -- but there are critical fundamental differences that make them not interchangeable. Men cannot bear children, for example.

Exercise intolerance/fatigue and PEM have some similarities, but they are not the same thing. ME/CFS research using CPET testing has clearly demonstrated this. It's not a question of minor differences or severity. The two are different entities.

As long as you insist on conflating the common symptoms exercise intolerance and fatigue with PEM, any further conversation on this topic is pointless. You will continue to insist that because fatigue is a feature of sickness behavior, then PEM is a feature of sickness behavior, and I will continue to insist that fatigue, even extended fatigue, is not PEM. We will make no further progress. It's time to end this discussion and wait for the research to catch up.

 

[Sidereal]

I think they looked at the short and long term cases but didn't see the same elevated / decreased pattern that they found in plasma. I think that either Hornig or Lipkin commented. I'll post the link if I find it.

In this study they only had 32 ME/CFS patients so unless the effect is really big you're not going to pick it up when you divide 32 patients into two groups ( <3 years or >3 years).

 

[SOC]

It would be interesting to know why some of us don't develop PEM until 6-7yrs into the illness, such as myself, even during the acute viral phase. Sickness behaviours are an acute adaptive mechanism.

An interesting question is whether 2-day CPET testing would show metabolic abnormalities early in the illness even before the patient recognizes what we call PEM. Maybe PEM doesn't arise until later, or maybe the metabolic problems exist but are subtle earlier in the illness in some patients. I'd love to see some research on that topic.

 

[Sidereal]

The authors of the Maes study stated that they think PEM probably also occurs during sickness behavior.

That's not a study, it's a narrative review. An opinion piece essentially.

 

[Scarecrow]

In this study they only had 32 ME/CFS patients so unless the effect is really big you're not going to pick it up when you divide 32 patients into two groups ( <3 years or >3 years).

Very true but in the plasma study, because cytokines were up in short term and down in long term patients, there was no significance between patients and controls without stratifying by duration. So it may be relevant that the CSF results still showed significance without the stratification.

 

[Sidereal]

Very true but in the plasma study, because cytokines were up in short term and down in long term patients, there was no significance between patients and controls without stratifying by duration. So it may be relevant that the CSF results still showed significance without the stratification.

Right, or it could be that the CSF sample contained too few short duration patients to influence results.

 

[Hip]

This is not a quantitative issue -- more or less severe. This is a qualitative issue. Exercise intolerance and fatigue, which is what is seen in cancer, is not the same thing as PEM. Cancer patients can exercise and benefit from it. CPET tests are commonly done on cancer without adverse effects. The CPET result abnormalities seen in ME/CFS patients are not reported in cancer patients. See Cardiopulmonary exercise testing in cancer rehabilitation: a systematic review..

Firstly, if you had actually read my above post, you would have seen that I offered an explanation of why the PEM in ME/CFS may be qualitatively different from the PEM in cancer. I am not going to repeat what I said.

Secondly, one major flaw in your argument is that not all cancer patients get fatigue. It depends on the status of the cancer. The review you quoted offers no indication of the level of fatigue present in these cancer patients; if the fatigue was only light, exercise may well have benefited them, just as exercise can benefit mild ME/CFS patients.

Thirdly, the 2-day CPET testing in ME/CFS patients may not just be measuring PEM, it may also be affected by the OI problems in ME/CFS. So this testing may not be a pure measure of PEM.

Your position that the exercise intolerance/fatigue seen in many different conditions is equivalent to ME/CFS PEM

Can kindly stop misrepresenting my views. I did not say that.

That's not a study, it's a narrative review. An opinion piece essentially.

Can you explain, Sidereal, how you think listing and comparing ME/CFS symptoms and sickness behavior symptoms amounts to an opinion!?

This is a careful study of these symptoms, and a careful consideration of similarity as dissimilarities between them.

 

[Mij]

@SOC My experience is that the abnormalities are there right from the beginning. I was pretty much feeling 80+% when I started to do more activities when PEM slowly started, it wasn't too bad at first but got progressively worse the more I did- permanently. I never went back to baseline.

It would be very interesting if the CPET 2 day test picked this up earlier on.